Microvalve-assisted patterning platform for measuring cellular dynamics based on 3D cell culture.
A microfluidic platform to satisfy both 3D cell culture and cell-based assay is required for credible assay results and improved assay concept in drug discovery. In this article, we demonstrate a microvalve-assisted patterning (MAP) platform to provide a new method for investigating cellular dynamics by generating a linear concentration gradient of a drug as well as to realize 3D cell culture in a microenvironment. The MAP platform was fabricated by multilayer soft lithography and several microvalves made it possible to pattern a cell-matrix (scaffold) and to exchange media solutions without breaking cell-matrix structure in a microchannel. This approach provides not only exact fluids control, bubble removal, and stable solution exchange in a microchannel, but also reliable scaffold fabrication and 3D cell culture. In this study, hepatotoxicity tests with human hepatocellular liver carcinoma cells (HepG2) were also performed in real-time monitoring where cell morphologies exposed to different drug concentrations were observed at a time. Compared to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, the MAP platform could be used to reduce drug amount and assay time for cell-based assays as much as 10 and 3 times, respectively.
Kim
Minseok S
MS
Department of Bio and Brain Engineering, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon 305-701, Korea.
Lee
Wonhye
W
Kim
Yu Chang
YC
Park
Je-Kyun
JK
D001681:Biological Assay / Q000295:instrumentation*; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D045744:Cell Line, Tumor; D002470:Cell Survival; D004867:Equipment Design; D000431:Ethanol; D017022:Flow Injection Analysis / Q000295:instrumentation; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D044085:Microfluidics / Q000295:instrumentation; D008846:Micromanipulation / Q000295:instrumentation; D054457:Tissue Scaffolds
D000431:Ethanol